The clinical utility of molecular diagnostics in breast cancer management: using biomarkers to optimize personalized medicine

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Abstract

Significant improvement in the delivery of breast cancer care has been made in the last decades and new (targeted) treatments became available on the market. However, improving the ability to identify tumor characteristics, may potentially even further reduce over- and under treatment or decrease costs. Several initiatives have focused on the use of prognostic or predictive molecular biomarkers that may guide the treatment of breast cancer patients.

In current clinical practice, tissue biopsies are used to determine biomarker expression and thereby characterize the tumor. However, obtaining tissue biopsies is invasive and consequently is not suitable to repeatedly assess tumor characteristics. Furthermore, potential sampling errors, tumor heterogeneity and the potential of tumors to change over time may result in divergent tumor profiles when repeatedly sampling tissue from solid tumors. In order to increase the probability of capturing the full tumor profile, new technologies may be required. An innovative field aiming to develop a technology that is less invasive and suitable to capture potential tumor heterogeneity, is focusing on the use of liquid biopsies. Such innovative techniques can, however, only be successfully implemented in clinical practice when their clinical utility has been demonstrated in clinical trials.

In this thesis, the clinical utility of molecular biomarkers in breast cancer management was evaluated. It demonstrated that traditional diagnostics are less frequently performed on both, tumor biopsy and tumor resection material, than expected. When tests were performed on both materials, the results are usually concordant. Still, new methods such as liquid biopsies, suitable to frequently obtain tumor biopsies, are required. While liquid biopsies are thought to be promising, the majority of studies focusing on liquid biopsies is not sufficiently focusing on evaluating their clinical utility, which is necessary before new diagnostics will be implemented in clinical practice. To date, the clinical utility of new liquid biopsies is only evaluated in the STIC METABREAST trial. Though the clinical outcomes have shown that using circulating tumor cells to guide either chemotherapy or endocrine therapy in metastatic breast cancer is non-inferior, the health economic outcomes demonstrated that this strategy is not cost-effective when considering short term outcomes.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • IJzerman, Maarten J., Supervisor
  • Koffijberg, Erik, Supervisor
Award date10 Jan 2020
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-4906-6
DOIs
Publication statusPublished - 10 Jan 2020

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